MRI of the breast: state of the art

Contrast-enhanced MRI of the breast is probably the most sensitive method to detect breast pathology. It is best used to improve the sensitivity of mammography and sonography in selected patient groups with high breast cancer prevalence, where conventional methods are known to be less sensitive. Despite the high sensitivity of MRI, 5-12 % of invasive carcinomas are not recognized during MRI, because of lack of the typical criteria of carcinoma. MRI is probably inferior to mammography in detecting ductal in-situ carcinoma or very small carcinomas (< 3 mm), because the neo-angiogenesis induced by these small carcinomas is too faint to be detected by contrast-enhanced MRI. These tumours cannot be excluded by a normal MRI examination. MRI is non-specific as the distinction of benign and malignant breast lesions is unreliable. Only in selected cases (fat- or blood-containing lesions) may it improve the specificity of mammography and sonography. Mostly image-guided core biopsy is by far the most specific and least expensive method to establish a definitive diagnosis. For lesions exclusively detected by contrast-enhanced MRI, simple and reliable localisation devices are urgently needed. Presently accepted indications for MRI of the breast are: patients with silicone implants after mastectomy or augmentation mammoplasty (detection of recurrence/prosthesis rupture/silicon leakage); patients whose breasts are difficult to evaluate by combined mammography and sonography, who have had breast conservation therapy (local recurrence), or who have proven carcinoma in one breast (multifocality/-centricity or contralateral breast carcinoma) or proven axillary lymph node metastases from an unknown primary tumor, especially when these are hormone receptor positive; patients with extensive postoperative scarring. In the future, genetically defined high breast cancer risk may become an indication.     

Contrast-enhanced MRI of the breast: accuracy, value, controversies, solutions

OBJECTIVE: Contrast-enhanced MRI of the breast has been one of the most controversial areas of MRI. Even though most investigators have, in selected indications, been able to improve accuracy by the additional use of contrast-enhanced MRI, its abuse has been feared not only because of increased costs for imaging, but also because of increased biopsy rates caused by false positive calls and because of errors caused by insufficient standardisation. In this article an overview is given of the present knowledge about contrast-enhanced MRI of the breast. Factors that influence the accuracy and reproducibility of contrast-enhanced MRI are analysed. METHOD: Factors that influence accuracy include: (1) technical factors that influence accuracy, e.g. slice thickness (partial volume effect), motion reduction, reduction of (cardiac) artifacts, dosage of contrast agent, choice of pulse sequence and echotime, and choice of the method for elimination of fat signal. (2) Hormonal factors (timing of the examination with reference to the menstrual cycle, hormonal replacement therapy). They influence accuracy and must be taken into account. (3) Interpretation guidelines-their choice influences sensitivity and specificity mostly inversely and the use of information from conventional imaging appears necessary. (4) Patient selection influences accuracy for statistical and for biological reasons. RESULTS: Based on the present literature and on the experiences gathered in six German universities (> 12000 examinations) an excellent sensitivity (> 98%) can be achieved for the combination of mammography and MRI. However, specificity strongly varies with the indications. Recommended indications include examination of breasts with impaired evaluation due to severe scarring, after silicon implants and in the dense breast, exclusion of multicentricity and search for primary tumor. Indications under investigation include high risk patients and strictly selected problem cases. CONCLUSION: If appropriately applied and used for selected indications, contrast-enhanced MRI may allow a significant diagnostic gain. In order to take advantage of the full potentials of contrast-enhanced MRI the development of commercially available biopsy coils is essential.     

Scintigraphic imaging of breast cancer: a review

Scintimammography is a recently verified technique that will expand the use of nuclear medicine to a new group of patients in whom scintigraphic imaging has not been widely used. If performed correctly, and in certain groups of patients, it delivers a sensitivity as high as X-ray mammography or magnetic resonance imaging (MRI) in palpable tumours but with greater specificity. It is best used in patients in whom X-ray mammography, ultrasound and MRI prove non-diagnostic or unhelpful, particularly those women with dense breasts or who have had previous breast surgery. The mechanism of uptake of 99Tcm-MIBI in breast tissue is only partly understood and in itself may help in determining important aspects of tumour function, such as the response to cytotoxic chemotherapy. Other scintigraphic methods for imaging breast cancer may be able to look at other aspects of cancer function, for example blood supply, metabolic rate or the in vivo assessment of oestrogen or somatostatin receptor status. This in turn may be useful in planning treatment. Metastatic disease may best be monitored with 18F-FDG PET, which has a sensitivity greater than MRI but a similar specificity. Much furtner work will need to be done on the use of nuclear medicine in breast cancer, but the addition of unique functional information to the anatomical data from X-ray and MRI should benefit future patients' management.     

Analysis of dynamic MR breast images using a model of contrast enhancement

We describe a model of dynamic contrast enhancement in breast MRI designed to aid the radiologist in cases for which X-ray mammography is ineffective. The breasts are segmented from the image slices by a dynamic programming algorithm after morphological opening. A pharmacokinetic model has been derived to fit the rise in intensities after injection of a contrast agent, in a way that facilitates investigation of the effects of different models of bolus injection. The pharmacokinetic model is used in a modified Horn-Schunck algorithm to correct for motion effects during the seven minute acquisition period. The results show significant localization of tumours and enable discrimination of cancerous tissue. In particular, we illustrate the approach with an image that shows a carcinoma, whose appearance and localization are greatly improved by the registration algorithm.     

Breast carcinoma: MR imaging before re-excisional biopsy

PURPOSE: To investigate the role of magnetic resonance (MR) imaging in the examination of patients after excisional biopsy of breast carcinoma before re-excision. MATERIALS AND METHODS: Forty-seven patients underwent contrast material-enhanced MR imaging after initial excisional biopsy of breast carcinoma before further surgery. RESULTS: The positive predictive value of MR imaging for predicting residual disease was 82%; the negative predictive value was 61%. Fourteen patients had multifocal (n = 6) or diffuse (n = 8) carcinoma. The extent of tumor was correctly identified with MR imaging alone in nine of the 14 patients, with both mammography and MR imaging in three patients, with mammography alone in one patient, and with no imaging modality in one patient. In four of the 14 patients, management was altered from re-excision to mastectomy (n = 3) or from breast-conservation therapy to mastectomy (n = 1). CONCLUSION: MR imaging has a high positive predictive value for predicting residual tumor after excisional biopsy. The identification of mammographically and clinically unsuspected multifocal or extensive residual tumor may lend support for mastectomy rather than re-excision. However, false-negative findings due to postsurgical changes and false-positive findings due to enhancement of granulation tissue and benign breast tissue remain limitations.     

Use of 99Tcm-MIBI in the assessment of patients with suspected recurrent breast cancer

A prospective trial was performed to assess the accuracy of 99Tcm-methoxyisobutyl isonitrile (99Tcm-MIBI) scintimammography and X-ray mammography in 18 patients (mean age 58 years, range 46-79 years) with suspected recurrent breast cancer in the breast and/or loco-regional tissues. All patients had been diagnosed to have breast cancer 1-23 years before scintimammography. Two patients had undergone mastectomy, so that a total of 34 breasts were studied with X-ray mammography and with prone-lateral and anterior scintimammography. Any abnormalities on X-ray mammograms and scintimammograms were noted, as was any additional local or nodal uptake of 99Tcm-MIBI. The nature of any lesion seen with either modality, or in which there was a clinical suspicion of recurrence, was confirmed by cytological or histological examination of tissue samples. There were nine breasts with recurrent cancer in eight patients. X-ray mammography identified six of these cancers. 99Tcm-MIBI scintimammography identified eight of nine recurrent breast cancers (the one cancer not seen was positive on X-ray mammography). In the 26 breasts without cancer, two were reported as having changes consistent with cancer and one was reported equivocal. There were three false-positive and one equivocal scintimammograms. The accuracy of 99Tcm-MIBI scintimammography within the breast (85%) was similar to X-ray mammography (82%). Axillary lymph node recurrence occurred in five patients, four of whom were positive with 99Tcm-MIBI. An additional patient had focal uptake of 99Tcm-MIBI at the site of recurrent cancer on the anterior chest wall. In conclusion, 99Tcm-MIBI scintimammography may provide useful complementary information in patients with suspected recurrence of cancer in the breast or loco-regional tissues.     

Vascularity of proliferative breast disease and carcinoma in situ correlates with histological features

The level of vascularity within an invasive breast carcinoma is a predictor of metastatic potential and survival. However, little is known about the vascular potential and prognostic value of angiogenesis in preinvasive breast pathology. Women with proliferative breast disease or carcinoma in situ are at increased risk of developing invasive breast cancer. This relative risk increases in correlation with defined histopathological features. We asked whether these early proliferative lesions and carcinoma in situ were capable of inducing a vascular supply. Vascularity in preinvasive archival paraffin-embedded breast tissue from 90 patients was quantified by immunohistochemical identification of vessels using anti-von Willebrand factor. Vascular scores were analyzed with respect to histopathological diagnosis, age at diagnosis, and presence of coincident invasive disease. These data indicate that: (a) the vascularity of histopathologically normal epithelium is greater in breasts containing invasive disease than in breasts lacking invasive disease; (b) simple proliferative breast disease induces a vascular supply greater than that of normal breast epithelium; and (c) vascularity increases in proportion to epithelial lesion progression and relative risk of invasion. These studies indicate that the vascularity of preinvasive breast pathology may be a clinically useful predictor of invasive breast cancer.     

FDG PET evaluation of granular cell tumor of the breast

Granular cell tumor is a rare, usually benign neoplasm of neural origin that may arise in virtually any site and, when situated in the breast, can mimic breast carcinoma. We describe a case of granular cell tumor of the breast in a 57-yr-old woman. Clinical evaluation, mammography, sonography and MRI suggested a carcinoma with infiltration of skin and muscle. However, the tumor did not display increased glucose metabolism on PET. Clinical findings, imaging results, histological characteristics and surgical management are discussed.     

Serendipity in diagnostic imaging: magnetic resonance imaging of the breast

BACKGROUND: Magnetic resonance imaging (MRI) of the breast has been proposed as a noninvasive diagnostic test for evaluation of suspicious ("index") lesions noted on mammography and/or clinical breast examination (CBE). However, women may have incidental ("serendipitous") lesions detected by MRI that are not found on mammography or CBE. To understand better whether or not biopsy procedures should be performed to evaluate serendipitous lesions, we estimated the breast cancer risk for women with this type of lesion. METHODS: A decision analysis model was used to estimate the positive predictive value (i.e., the chance that a woman with a serendipitous lesion has cancer) of MRI for serendipitous lesions in women who had an abnormal mammogram and/or CBE suspicious for cancer (where a biopsy procedure is recommended). We restricted the analysis to data from women whose index lesions were noncancerous and used meta-analysis of published medical literature to determine the likelihood ratios (measures of how test results change the probability of having cancer) for MRI and the combination of CBE and mammography. The positive predictive value of MRI was calculated using the U.S. population prevalence of cancer (derived from registry data) and the likelihood ratios of the diagnostic tests. RESULTS: Under a wide variety of assumptions, the positive predictive value of MRI was extremely low for serendipitous lesions. For instance, assuming sensitivity and specificity values for MRI of 95.6% and 68.6%, respectively, approximately four of 1000 55- to 59-year-old women with serendipitous lesions would be expected to have cancer (positive predictive value = 0.44%, 95% confidence interval = 0.24%-0.67%). CONCLUSION: In women with a suspicious lesion discovered by mammography and/or CBE that is found to be benign, serendipitous breast lesions detected by MRI are extremely unlikely to represent invasive breast cancer. Immediate biopsy of such serendipitous lesions may, therefore, not be required.     

Uterine artery embolization for the treatment of uterine fibroids

Masking bias is hypothesized to explain associations between breast density and breast cancer risk. Tumours in dense breasts may be concealed at the initial examination, but manifest themselves in later years, suggesting an increase in breast cancer incidence. We studied the association between breast density and breast cancer risk in 0, 1-2, 3-4 and 5-6 year periods between initial examination and diagnosis. We studied 359 cases and 922 referents, identified in a breast cancer screening programme in Nijmegen, The Netherlands. Breast density was assessed at the initial examination and classified as 'dense' (if > 25% of the breast was composed of density) or 'lucent' (< or = 25% density). In women examined with mid-1970s film screen mammography, we found that at time 0 the odds ratio (OR) for women with dense breasts compared to those with lucent breasts was 1.4 (95% confidence interval (CI): 0.7-6.2). After a 3-4 year period the risk was increased to 3.3 (95% CI: 1.5-7.1). Then, the risk decreased again (OR: 1.2, 95% CI: 0.6-2.7). This rise and decline in risk are in accordance with the masking hypothesis. The observation, however, that the risk at time 0 does not appear to be lower for women with dense breasts than for those with lucent breasts, seems to be inconsistent with the masking hypothesis and may be indicative of causality. The same analysis were performed in women whose initial screening examination was done with current high-quality mammography. Due to the small size of this study group no firm conclusions could be drawn, but it seems as if masking bias could still play a role with high-quality mammography.     

Magnetic resonance imaging in breast cancer staging

For many solid carcinomas, high-resolution cross-sectional imaging has changed cancer staging, the evaluation of therapeutic response, the detection of recurrence, and even how therapy is selected and performed. Such imaging has not yet had similar effects on breast cancer. Evaluations of therapeutic response in breast carcinomas have been impeded by the current limited methods of evaluating breast tumor size and extent: clinical palpation, ultrasonography, and mammography. The use of magnetic resonance imaging (MRI) of the breast in the evaluation of breast tumors brings the advantages of high-resolution cross-sectional imaging to breast cancer staging and treatment evaluation and is likely to greatly enhance research efforts in this complex disease. MRI of the breast has evolved to be the most accurate noninvasive technique for local staging of breast cancer. MRI is most accurate in measuring tumor size and detecting multicentric disease. These staging characteristics affect the selection of therapy and initial determination of prognosis; therefore, MRI of the breast can change the assessment of fundamental parameters on which treatment is selected. Because clinical trials of new cancer treatments are predicated on proper and accurate characterization of the tumor, MRI also should affect how clinical trials are performed and evaluated.     

Angiogenic potential of malignant and non-malignant human breast tissues in an in vivo angiogenesis model

Tumors need to acquire an angiogenic phenotype for outgrowth and metastasis formation. Limited information on the angiogenic potential of specific tissues, especially human breast tissues is available. Here we describe an in vivo model, using the dorsal skin fold chamber in immunodeficient nude mice, where various tissues of human breast origin were xenografted and evaluated for their angiogenesis-inducing potential. We found that angiogenesis was abundantly induced by all breast carcinoma tissue samples. Similar angiogenesis was induced by tissue samples from breasts with hyperplasia and apocrine metaplasia. Histologically normal tissues adjacent to the tumor induced angiogenesis in 66% of the cases. Angiogenesis was not induced by control tissues from normal healthy breasts, obtained after cosmetic breast reduction. Angiogenesis induction parallelled VEGF production by the tumor cells. The tissue induced neovascularization, found both around and in the human tissue, was functional since a tail vein injection of albumin-FITC revealed positive tumor microcirculation within 5 min, while the tumor tissue still consisted of vital human epithelial cells after 14 days.     

Scintimammography with technetium-99m methoxyisobutylisonitrile: comparison with mammography and magnetic resonance imaging

The aim of the study was to compare the diagnostic accuracy of scintimammography with technetium-99m methoxyisobutylisonitrile (MIBI; SMM) in the detection of primary breast cancer with that of mammography (MM) and magnetic resonance imaging (MRI). Fifty-six patients with suspected lesions detected by palpation or MM were included in the study. Within the 4 weeks preceding excisional biopsy, MM and MRI were performed in all patients. Between 5 and 10 min after the injection of 740 MBq 99mTc-MIBI, SMM in the prone position was performed. In the total group of 56 patients, 43 lesions were palpable, while 13 were non-palpable but were detected by MM. Breast cancer was confirmed by histopathology in 27 of the patients (22 palpable and 5 non-palpable carcinomas). The tumour size ranged from 6 to 80 mm in diameter. For non-palpable lesions, the sensitivity of SMM, MM and MRI was 60%, 60% and 100%, respectively, while the specificity was 75%, 25% and 50%, respectively. For palpable breast lesions, all methods showed high sensitivity (SMM 91%, MM 95%, MRI 91%) but SMM demonstrated significantly higher specificity (SMM 62%, MM 10%, MRI 15%). In two mammographically negative tumours (dense tissue), SMM showed a positive result. In comparison to MRI, one additional carcinoma could be diagnosed by SMM. It may be concluded that for palpable breast lesions, the diagnostic accuracy of SMM is superior to that of MM and MRI. Through the complementary use of SMM it is possible to increase the sensitivity for the detection of breast cancer and multicentric disease. In patients in whom the status of a palpable breast mass remains unclear, SMM may help to reduce the amount of unnecessary biopsies.     

The role of 99mTc-sestamibi and other conventional radiopharmaceuticals in breast cancer diagnosis

The wide availability and the extensive use of screening mammography have resulted in an earlier diagnosis of breast cancer and in a significant reduction in the relative risk of dying from this disease. Despite technical improvements and major advantages associated with the use of mammography (and breast ultrasound), this procedure has some limitations in clinical practice, especially in women with dense breast tissue, implants, severe dysplastic disease, or significant architectural distortion following breast surgery or radiation therapy. Different noninvasive imaging techniques have been evaluated to overcome these limitations. Nuclear medicine also has been actively involved in the detection of breast cancer, using various types of radiopharmaceuticals. Currently, there are three radiotracers commonly used for breast imaging or scintimammography in either clinical practice or research: 99mTc-sestamibi and 99mTc-tetrofosmin (two agents used for myocardial perfusion imaging) and 99mTc-MDP (methylene diphosphonate, used for bone scintigraphy). 99mTc-sestamibi was the first radiopharmaceutical to be approved by the FDA for scintimammography. Several prospective studies have shown that the overall sensitivity of 99mTc-sestamibi scintimammography in detection of breast cancer was 85%, the specificity was 89%, and the positive and negative predictive values were 89% and 84% respectively. Similar numbers have been demonstrated for 99mTc-tetrofosmin and 99mTc-MDP scintimammography. Although not indicated as a screening procedure for the detection of breast cancer, scintimammography may play a useful and significant role in various specific clinical indications such as nondiagnostic or difficult mammography, and evaluation of high-risk patients, tumor response to chemotherapy, and axillary lymph node metastatic involvement.     

Outcomes of modern screening mammography

The University of California, San Francisco, Mobile Mammography Screening Program is a low-cost, community-based breast cancer screening program that offers mammography to women of diverse ethnic backgrounds (36% nonwhite) in six counties in northern California. Analysis of data collected on approximately 34,000 screening examinations from this program shows that the positive predictive value and sensitivity of modern screening mammography to be lower for women aged 40 to 49 years compared to women aged 50 and older. This lower performance is due to the lower prevalence of invasive breast cancer in younger women and possibly to age differences in breast tumor biology. Because of this lower performance, women in their forties may be subjected to more of the negative consequences of screening, which include additional diagnostic evaluations and the associated morbidity and anxiety, the potential for detecting and surgically treating clinically insignificant breast lesions, and the false reassurance resulting from normal mammographic results. Since the evidence is not compelling that the benefits of mammography screening outweigh the known risks for women aged 40 to 49 years, women considering mammography screening should be informed of the risks, potential benefits, and limitations of screening mammography, so that they can make individualized decisions based on their personal risk status and utility for the associated risks and potential benefits of screening.     

Magnetic resonance imaging]

During the last ten years substantial improvement of hardware and software used for the construction of MRI scanners has made available MRI sequences with high temporal and spatial image resolution. Therefore, MR imaging has become an excellent tool and in certain cases the gold standard for the evaluation of cardiovascular diseases. Primary indications for cardiovascular MRI include the assessment of aortic diseases, the arrhythmogenic right ventricle, surgically corrected congenital heart diseases, pericardial disease, intra- and paracardiac tumors and quantification of ventricular function and volumes and myocardial mass. Secondary indications include hypertrophic and dilative cardiomyopathies, valvular and ischemic heart disease. MRI is a totally noninvasive diagnostic technique which is safe and without known harmful potential to biological tissue. The wide diagnostic spectrum providing anatomical, geometrical functional and biochemical information cannot be accomplished by any other diagnostic method.     

Treatment outcome with radiation therapy after breast augmentation or reconstruction in patients with primary breast carcinoma

BACKGROUND: Analyses were performed to determine local control and cosmetic outcome of breast carcinoma patients with prosthetically augmented or reconstructed breasts who had received radiation therapy (RT). METHODS: Twenty-one newly diagnosed breast carcinoma patients with prosthetically augmented or reconstructed breasts were treated with external beam RT. All patients received whole breast RT (median dose, 50.4 gray [Gy]) and 19 were boosted to a median dose of 60.4 Gy. A median dose of 50.4 Gy was delivered to the regional lymph nodes in 12 patients. Tissue equivalent bolus material was used in six patients. Seventeen patients received adjuvant systemic therapy. Cosmetic results were evaluated at 3-6-month intervals. RESULTS: With a median follow-up of 32 months, good/excellent cosmetic results were observed in 71% of patients (100% in those with augmented breasts and 54% in those with reconstructed breasts). Four patients (19%) with fair/poor cosmetic outcomes required implant removal and/or revision. Multiple clinical and treatment-related factors were analyzed for their impact on cosmetic outcome. A worsened cosmetic result was observed with increasing stage (P = 0.076), breast reconstruction (vs. augmentation) (P = 0.030), and bolus application (P = 0.016). All patients with fair/poor cosmetic outcomes had time intervals from implant insertion to RT ranging from 53-213 days. Two patients developed an isolated local recurrence within the augmented breast. CONCLUSIONS: Patients with prosthetically augmented breasts can undergo RT and expect good/excellent cosmetic results. Patients with reconstructed breasts are at a significantly greater risk for cosmetic failure. This risk may be related to the higher percentage of patients with advanced disease, those who received bolus application, and those who received earlier delivery of RT (after the cosmetic procedure) in reconstructed breasts.     

Synchronous, bilateral mastectomy

Sixty-four patients (mean age, 51 years) had mastectomies which were synchronous and bilateral. Sixty-one premastectomy biopsies (bilateral, 34 and unilateral, 27) demonstrated the following: invasive carcinoma, 17; noninvasive carcinoma, 24; combination of above, 10; and benign disease, 10. Twenty-two patients had bilateral mastectomy because of bilateral positive biopsy. Twenty-nine patients with unilateral carcinoma on biopsy had bilateral mastectomy. Thirteen patients had bilateral mastectomy despite benign disease only on biopsy (10) or no biopsy (3). Ten unexpected carcinomas (34%) were found in the contralateral breast in the 29 patients with carcinoma diagnosed on unilateral biopsy. The biopsy pathology of these 10 specimens was invasive ductal carcinoma in 1 and multifocal, noninvasive carcinoma (ductal, 3 and lobular, 6) in 9. An unexpected carcinoma may be found in the contralateral breast in a significant number of patients who are selected for bilateral mastectomy, particularly if the selection is on the basis of a noninvasive, lobular histology. Bilateral mastectomy may be appropriate for such patients, particularly when complicated by a strong family history and breasts which are difficult to assess by physical or mammographic examination.     

MR lesion detection in a breast cancer population

Implementation of MR imaging of the breast as an extension of the existing imaging modalities in the diagnosis of breast cancer was evaluated in a university cancer center, MR imaging of the breast was performed in 54 patients, in whom the MR results were compared with the triple test (the combination of clinical examination, mammographic evaluation, and cytology) and the final histological diagnosis. MR imaging of the breast depicted 30 of the 33 malignancies (sensitivity, 91%). In two of the malignancies, the carcinoma was clinically and mammographically occult. For the three patients with a false-negative MRI diagnosis, the conventional mammography showed suspicions clustered microcalcifications as a sign of in situ carcinoma. For seven patients, MR imaging of the breast incorrectly suggested the presence of a malignant lesion (specificity, 67%). To improve MR specificity, we perform MR-guided ultrasonographic fine-needle aspiration biopsy (FNAB). Although MR imaging of the breast is a highly sensitive examination, conventional x-ray mammography remains the most efficient imaging modality in the diagnosis of breast cancer. In our patient population, MR imaging of the breast had additional value for women with mammographically dense breast tissue and especially for patients with clinical evidence of breast carcinoma that could not be detected with conventional diagnostic methods.